The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the present invention.
Human papillomavirus (HPV) is a generic name for a group of epithelial cell specific viruses which have a diversity of DNA restriction enzyme profiles and different capsid protein antigenicity. Such viruses show similar shapes and are widespread in human and animals. They are highly specific, without cross-species transmission. Up to now, the number of defined types of HPV is more than 110. They are grouped into high-risk types and low-risk types, based on the correlation of the HPV types and oncogenic risks. Low-risk type HPVs, e.g., HPV6, 11, 42, 43, 44, often cause benign lesions, such as external genital warts. High-risk type HPVs, e.g., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, are associated with the developments of cervical cancer and cervical intraepithelial neoplasm (CIN). Research on specimens from worldwide cervical cancer tissues indicated that HPV16 and 18 have the highest infection rates. Among all of the detected types, HPV16 accounts for 50%, HPV18 for 14%, HPV45 for 8%, HPV31 for 5% and HPVs of other types account for 23% of infections. The HPV viral genome consists of three gene regions: early region (E), late region (L) and non-coding upstream regulatory region (URR), in which the early region comprises six early open reading frames, respectively defined as E1, E2, E4, E5, E6 and E7. Proteins E6 and E7 are oncoproteins, and play an important role in viral replication and immortalization and transformation of cells (Park et al., Cancer 76:1902-1913 (1995)).
One early region gene, E7, encodes a small polypeptide with a molecular weight of about 10 KD, which can bind to a gene expression product of retinoblastoma, Rb. Rb is a tumor suppressor, which can bind to transcription factor E2F and inactivate it. E2F regulates the transcription of many growth related genes. The formation of Rb-E2F complex prevents the expression of these genes in G0 and G1 phases, and thus limits their expression to S phase. In S phase, Rb-E2F complex is “programmed” to be disassociated, so as to release active transcription factor E2F. The formation of Rb-E7 complex will prevent the formation of Rb-E2F complex and shorten S phase, i.e., promote the cell cycle progression. E7 protein of HPV types with high oncogenicity has a higher affinity to Rb when compared to E7 protein of non-tumorigenic HPV types.